In this study, pindolol, a beta-adrenoceptor blocking agent marketed as a racemic mixture, was used as a model compound to investigate stereoselective renal clearance of organic cations in human beings. Six normal subjects received an oral dose of 20 mg racemic pindolol. Heart rate and blood pressure were measured throughout the study. A stereospecific high performance liquid chromatographic procedure was used to quantitate the concentrations of d- and l-pindolol in plasma and urine. Renal clearance and other pharmacokinetic parameters of both enantiomers were calculated and compared. The renal clearance of l-pindolol was greater than that of d-pindolol in all subjects. The renal clearance (mean +/- SD) was 240 +/- 55 ml/min for l-pindolol and 200 +/- 51 ml/min for d-pindolol (P less than 0.01). Since stereoselective binding to plasma proteins was not observed, differences in renal clearance between d- and l-pindolol were caused by either stereoselective renal transport, or stereoselective renal metabolism. The area under the plasma concentration-time curve, the amount of drug excreted, and the half-life of l-pindolol were greater than those of d-pindolol, which suggests that pindolol was also eliminated stereoselectively by nonrenal routes. The slopes of the resting heart rate vs. the plasma concentration of l-pindolol were significantly less than zero and were significantly correlated to the pretreatment heart rate, which supports the hypothesis that intrinsic sympathetic tone largely determines the effect of pindolol on the resting heart rate. The observation that pindolol is eliminated stereoselectively by the kidney may have clinical implications for other racemic drugs that are renally eliminated.